马来酸桂哌齐特的新合成方法  

A novel synthesis of cinepazide maleate

作　　者：付德才[1] 刘畅[1] 康钰[1] 陈兴贺[1] 

机构地区：[1]河北科技大学化学与制药工程学院,河北石家庄050018

出　　处：《中国药物化学杂志》2010年第3期190-191,194,共3页Chinese Journal of Medicinal Chemistry

摘　　要：目的设计马来酸桂哌齐特新的合成路线。方法以3,4,5-三甲氧基肉桂酸为原料,先与氯化亚砜反应制备3,4,5-三甲氧基肉桂酰氯(3),3与六水哌嗪反应得到重要中间体1-(3,4,5-三甲氧基肉桂酰基)哌嗪(4),4与氯乙酰吡咯啶反应制得桂哌齐特后再与马来酸成盐,得到目标物马来酸桂哌齐特。结果与结论目标化合物的结构经核磁共振氢谱确证。新合成路线成本低廉,过量的哌嗪易于回收,总收率达43%,目标产物晶型稳定。Aim To design a new synthetic route to prepare cinepazide maleate.Methods 3,4,5-Trimethoxycinnamylic acid as starting material was reacted with thionyl dichloride firstly to give 3,4,5-trimethoxycinnamoyl chloride（3）.3 was reacted with piperazine hexahydrate to afford the key intermediate 1-（3,4,5-trimethoxycinnamoyl）piperazine（4）.4 was coupled with N-pyrrolidine chloracetamide and then treated with maleic acid in ethanol to give cinepazide maleate.Results and conclusion The structure of target compound was confirmed by 1H-NMR.This synthetic route had the advantage of low cost and the excess piperazine was easy to recycle.The total yield was 43% and the product crystalline form was stable.

关 键 词：马来酸桂哌齐特 钙通道阻滞剂 工艺改进 

分 类 号：TQ463.5[化学工程—制药化工]